A porous membrane patterning technique is provided. In one embodiment, a porous membrane may be patterned via printing on the porous membrane with a solvent such that the porous membrane collapses where the solvent is applied. In another embodiment, a patterned porous membrane may be formed by casting a solution including at least components of the porous membrane into voids of a casting plate or stencil, removing the casting plate, and letting the remaining components go through a phase inversion process to form porous membrane regions.
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1. A method for patterning a porous membrane, comprising:
receiving an input comprising a pattern, wherein the pattern defines a closed flow area; and
controlling a printer to apply a solvent to a surface of a porous membrane in the desired pattern such that the porous membrane collapses where the solvent is applied.
3. The method of
4. The method of
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The subject matter disclosed herein relates to porous membranes, such as nitrocellulose membranes, and, more particularly, to the formation of patterns on and with such membranes.
Porous membranes may be used as substrate materials for assays, including medical assays or environmental assays. For example, a porous membrane may include some or all of the assay components, e.g., antibodies or binding agents, that react with a sample and provide an output. In the example of a pregnancy test, the porous material is placed in contact with the sample fluid, which may then flow laterally along the porous membrane to contact the assay materials disposed on or within the porous membrane. Depending on the presence or absence of a particular compound, such as hCG, the sample will react with the assay components in the porous membrane to provide different visual outputs, depending on if the sample is from a pregnant or non-pregnant patient. In such an example, the assay components are arranged along the lateral flow path of the porous membrane. For more complicated assays, more complex flow paths and patterns may be involved. However, such patterns may be difficult to form, particularly in repeating patterns on larger sheets that are subsequently cut into single strips for individual use.
In one embodiment, system for patterning a porous membrane, is provided. The system includes a memory or storage device storing processor-executable instructions that, when executed by a processor, cause acts to be performed comprising: receiving an input corresponding to a desired pattern; and controlling a printer to apply a solvent to a surface of a porous membrane in the desired pattern such that the porous membrane collapses where the solvent is applied; and a processor configured to execute the instructions stored in the memory or storage device. The system also includes and a printer comprising a solvent application device configured to hold solvent and apply the solvent to the porous membrane in the desired pattern under control of the processor.
In another embodiment, a method for patterning a porous membrane is provided that includes receiving an input comprising a pattern; and controlling a printer to apply a solvent to a surface of a porous membrane in the desired pattern such that the porous membrane collapses where the solvent is applied.
In another embodiment, a method for patterning a porous membrane is provided that includes providing a casting solution comprising components that, when cast, form a porous membrane; applying the casting solution to a casting plate comprising a plurality of voids (e.g., in discrete or continuous formats), wherein the casting plate is positioned proximate to a substrate such that the casting solution directly contacts the substrate when applied within the voids; removing the casting plate; and allowing the casting solution to undergo a phase inversion process to form porous membrane regions only on portions of the substrate.
In another embodiment, a porous membrane is provided that comprises a repeating pattern printed on the porous membrane, wherein the repeating pattern comprises a repeat of an enclosed flow area bounded by a collapsed region of the porous membrane, wherein the collapsed region has a thickness of 0.02 mm to 0.35 mm in at least a portion of the collapsed region, and wherein the collapsed region is sufficiently collapsed to prevent a flow of fluid outside of the enclosed flow area.
These and other features, aspects, and advantages of the present invention will become better understood when the following detailed description is read with reference to the accompanying drawings in which like characters represent like parts throughout the drawings, wherein:
Porous membranes such as nitrocellulose membranes may be used for nucleic acid, protein, or other compound detection in diagnostic applications, e.g., food borne pathogen testing, medical testing, and drugs of abuse screening. Provided herein are methods for printing complex flow paths onto porous membranes that allow complex testing workflows to be translated to a lateral flow format. In certain implementations of the disclosed techniques, porous membranes with complex flow paths may be formed by selectively collapsing the membrane with solvent in the desired pattern. In another implementation, porous membranes may be formed by depositing membrane casting solution in the desired pattern or structure that facilitates the controlled deposition of regions with different size, morphology and/or chemistry. The porous membranes formed herein may have surface structures with 3D patterning at resolutions of 10-100 microns. Such fine detailing permits more complex flow pathways on the porous membranes that in turn allow more complex diagnostic tests to be performed in a cost-effective manner. The simple manufacturable preparation of custom flow paths in a lateral flow membrane is particularly beneficial for single-use, disposable testing implementations of complex testing work flows, such as nucleic acid testing.
The solvent may be any suitable solvent, such as an organic solvent or an ester-based solvent. In one embodiment, a volatile solvent may be used to facilitate rapid drying. The solvent may include, for example, one or more solvents such as solvents chosen from ketones, esters, ethers, hydrocarbons, and mixtures thereof. However, it should be understood that these are non-limiting examples of solvents that may be used in conjunction with the present techniques. Examples of such solvents may include one or more of methyl acetate, butyl acetate, ethyl acetate, isopropyl acetate, amyl acetate, propylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, diethylene glycol monoethyl ether acetate, ethyl-3-ethoxypropionate, 3-methoxybutyl acetate, 3-methyl-3-methoxybutyl acetate, methyl formate, ethyl formate, butyl formate, propyl formate, ethyl lactate, butyl lactate and propyl lactate.
In certain embodiments of the disclosure, printing may refer to contacting the porous membrane with the solvent. The solvent may be applied by any suitable printing method, without limitation, including manual application (e.g., via a syringe or stylet), stamping, gravure, piezoelectric, flexographic, pad, or inkjet printing. However, in particular embodiments, using a mechanized printer under processor-based control may permit finer pattern resolution relative to manual applications. For example, it is envisioned that the patterns as disclosed herein may define flow paths having a particular resolution in the micron scale, e.g., 100 microns or less.
An operator workstation 34 including the control circuitry 30 may be housed within the printer 22 or may be within a separate device. Regardless of whether the control circuitry 30 is within the printer 22, the system 20 may include additional processor-based components, various memory and/or storage components including magnetic and optical mass storage devices, internal memory, such as RAM chips. The memory and/or storage components may be used for storing programs and routines for performing the techniques described herein that are executed by the operator workstation 34 or by associated components of the system 20. Alternatively, the programs and routines may be stored on a computer accessible storage and/or memory remote from the printer 22 or the workstation 34 but accessible by network and/or communication interfaces present on the system 20. The computer 24 may also comprise various input/output (I/O) interfaces 36, as well as various network or communication interfaces. The various I/O interfaces may allow communication with user interface devices, such as a display 38, keyboard, mouse, etc., that may be used for viewing and inputting configuration information and/or for operating the system 20. The various network and communication interfaces may allow connection to both local and wide area intranets and storage networks as well as the Internet. The various I/O and communication interfaces may utilize wires, lines, or suitable wireless interfaces, as appropriate or desired.
In one embodiment, an operator may provide inputs to the printer 22 to specify the desired pattern for the porous membrane. Accordingly, the system 20 may be configured to store and execute software that facilitates drawing or pattern creation by the operator. Such software may include graphics software such as Adobe Illustrator, available from Adobe System Incorporated (San Jose, Calif.) or CorelDRAW® from Corel Corporation (Ottawa, Calif.). The workstation 34 may be configured with the appropriate processing circuitry for such software. In another embodiment, the operator may select from one or more stored patterns or flow paths. For example, an operator may select a particular flow path associated with a desired assay type. In addition, the operator may select a pattern, but customize its size and/or length to the resolutions permitted by the printer 22 to quantify certain features of flow path to achieve a desired result, such as assay time, desired assay component loading amount, desired sample loading amount, etc. After receiving the instructions from the control circuitry 30, the printer can apply the solvent in the desired pattern and to modify the pre-formed porous membrane 28 to yield a patterned porous membrane 40.
Shown in
Nitrocellulose membranes are, for example, membranes that may be formed through an evaporative phase inversion process. A patterned membrane may also be discretely deposited via printing techniques (e.g., stencil or screen printing) onto a casting surface, rather than coating the entire process web and subsequently patterning after a uniform porous membrane has been formed. This additive process facilitates geometries beyond a flat sheet for nitrocellulose or other porous membranes, e.g., multi-dimensional (2D and 3D) geometries that deviate from the flat sheet.
Casting solution 80 includes components for the formation of a porous membrane, which may include a polymer solution for phase inversion (e.g., a polymer, solvent and nonsolvent solution, that when cast, forms a suitable porous membrane), solvents, and pore forming additives. The casting solution 80 is applied over the casting plate 70 and voids 72 to directly contact the exposed substrate 74 and fill the voids 72. The plate 70 is then removed and phase inversion is allowed through evaporation of solvent. The result is a dried porous membrane region 82 that is only present in the areas of the substrate 74 corresponding to the locations of the voids 72. In this manner, specific regions 82 of porous membrane may be formed on the substrate 74. In certain embodiments, the regions 82 form a sample flow area.
In
Cast porous membranes may also be further patterned via the solvent printing techniques disclosed herein.
At step 102, the sample is allowed to flow through the flow area to react with the assay components present in the porous membrane. In certain embodiments, the assay components may include immobilized ligands capable of binding an analyte present in the sample, e.g., via a sandwich assay or a competitive assay. The ligands may bind or be directly coupled to a signal generator that provides an observable output at step 104.
A sample may include any fluid or suspended solid sample suspected of containing an analyte of interest. Samples may represent any body fluid or fluids, an agricultural or other biological sample, or a non-biological fluid, such as an environmental sample.
Technical effects of the invention include a porous membrane with increased complexity and pattern resolution that may facilitate assays with greater complexity. Other technical effects include 3D patterning and/or layering of porous membranes to achieve different morphologies during manufacturing.
This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.
Zhou, Hongyi, Misner, Matthew Jeremiah, Nichols, Jason Michael
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Executed on | Assignor | Assignee | Conveyance | Frame | Reel | Doc |
Feb 10 2014 | ZHOU, HONGYI | General Electric Company | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 032408 | /0088 | |
Feb 18 2014 | MISNER, MATTHEW JEREMIAH | General Electric Company | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 032408 | /0088 | |
Feb 19 2014 | NICHOLS, JASON MICHAEL | General Electric Company | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 032408 | /0088 | |
Feb 28 2014 | General Electric Company | (assignment on the face of the patent) | / | |||
Mar 20 2020 | General Electric Company | GE Healthcare UK Limited | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 053981 | /0329 | |
Mar 31 2020 | GE Healthcare UK Limited | Global Life Sciences Solutions Operations UK Ltd | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 054300 | /0369 |
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